Lung inflammation caused by adenosine-5′-triphosphate is mediated via Ca2+/PKCs-dependent COX-2/PGE2 induction

Lee, I-Te; Lin, Chih-Chung; Lin, Wei‐Ning; Wu, Wanling; Hsiao, Li-Der; Yang, Che‐Hua

doi:10.1016/j.biocel.2013.05.006

Cited by 22 publications

(16 citation statements)

References 37 publications

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“…PKC serves as a modulator of cPLA 2 /COX-2 expression and activation in response to various stimulators. It has been found that PKC is involved in cPLA 2 and COX-2 expression in ATP-stimulated vascular smooth muscle cells and alveolar type II cells (31). In the present study, we demonstrated that stimulation of adiponectin leads to activation and translocation of PKC from cytosol to membrane.…”

Section: L264supporting

confidence: 69%

AdipoR-increased intracellular ROS promotes cPLA₂and COX-2 expressions via activation of PKC and p300 in adiponectin-stimulated human alveolar type II cells

Chen

Yang

Chang

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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Adiponectin, an adipokine, accumulated in lung system via T-cadherin after allergens/ozone challenge. However, the roles of adiponectin on lung pathologies were controversial. Here we reported that adiponectin stimulated expression of inflammatory proteins, cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), and production of reactive oxygen species (ROS) in human alveolar type II A549 cells. AdipoR1/2 involved in adiponectin-activated NADPH oxidase and mitochondria, which further promoted intracellular ROS accumulation. Protein kinase C (PKC) may involve an adiponectin-activated NADPH oxidase. Similarly, p300 phosphorylation and histone H4 acetylation occurred in adiponectin-challenged A549 cells. Moreover, adiponectin-upregulated cPLA2 and COX-2 expression was significantly abrogated by ROS scavenger (N-acetylcysteine) or the inhibitors of NADPH oxidase (apocynin), mitochondrial complex I (rotenone), PKC (Ro31-8220, Gö-6976, and rottlerin), and p300 (garcinol). Briefly, we reported that adiponectin stimulated cPLA2 and COX-2 expression via AdipoR1/2-dependent activation of PKC/NADPH oxidase/mitochondria resulting in ROS accumulation, p300 phosphorylation, and histone H4 acetylation. These results suggested that adiponectin promoted lung inflammation, resulting in exacerbation of pulmonary diseases via upregulating cPLA2 and COX-2 expression together with intracellular ROS production. Understanding the adiponectin signaling pathways on regulating cPLA2 and COX-2 may help develop therapeutic strategies on pulmonary diseases.

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Section: L264supporting

confidence: 69%

AdipoR-increased intracellular ROS promotes cPLA₂and COX-2 expressions via activation of PKC and p300 in adiponectin-stimulated human alveolar type II cells

Chen

Yang

Chang

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…The activation of EP1, which is coupled to Gαq, by PGE 2 activates phosphatidylcholine-phospholipase C and ultimately leads to an increase in intracellular Ca 2+ and activation of PKC [14]. Recent studies found that the activation of the EP1/PKC pathway induces gene transcription and protein synthesis of several key proteins that are involved in cell migration and invasion.…”

Section: Discussionmentioning

confidence: 99%

EP1 receptor is involved in prostaglandin E2-induced osteosarcoma growth

Niu

Liu

et al. 2019

Bosn J of Basic Med Sci

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Recent studies showed that the activation of prostaglandin (PG) receptor EP1 promotes cell migration and invasion in different cancers. The aim of this study was to investigate the role of EP1 in the proliferation of osteosarcoma (OS) cells in vitro and in vivo. EP1 mRNA and protein levels were analyzed by real-time RT-PCR and Western blot, respectively in human OS cell lines MG63, OS732, U-2OS, HOS and SAOS-2 compared to human fetal osteoblastic hFOB 1.19 cells. MG63 cells were treated with PGE2, EP1 specific agonist 17-PT-PGE2, 17-PT-PGE2 + EP1 specific antagonist SC51089, or DMSO (control). EP1R-siRNA or a non-silencing irrelevant RNA duplex (negative control) were used for the transfection of MG63 cells, followed by PGE2 treatment. Nude mice carrying MG63 xenografts were treated with SC51089 (2 mg/kg/day). MG63 cells/xenografts were analyzed by MTT assay, TUNEL assay, PKC enzyme activity assay, and Western blot (EP1 and apoptotic proteins), and tumor growth/volume was evaluated in mice. EP1 levels were significantly higher in OS cells compared to osteoblasts. PGE2 or 17-PT-PGE2 treatment increased the proliferation and decreased the apoptosis of MG63 cells. Inhibition of EP1 by SC51089 or siRNA markedly decreased the viability of MG63 cells. Similarly, SC51089 treatment significantly inhibited MG63 cell proliferation and promoted apoptosis in vivo. The silencing of EP1 receptor by siRNA or blockade of EP1 signaling by SC51089 activated extrinsic and intrinsic apoptotic pathways both in vivo and in vitro, as evidenced by increased levels of Bax, cyt-c, cleaved caspase-3, caspase-8 and caspase-9. EP1 appears to be involved in PGE2-induced proliferative activity of MG63 cells. Antagonizing EP1 may provide a novel therapeutic approach to the treatment of OS.

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“…A549 cells (human alveolar epithelial cell carcinoma) were cultured as previously described [ 55 ]. After confluence was reached, the cells were treated with 0.05% trypsin/0.53 mM EDTA for 5 min at 37 °C.…”

Section: Methodsmentioning

confidence: 99%

Leptin Promotes cPLA2 Gene Expression through Activation of the MAPK/NF-κB/p300 Cascade

Hsu¹,

Chang

et al. 2015

IJMS

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Hyperplasia or hypertrophy of adipose tissues plays a crucial role in obesity, which is accompanied by the release of leptin. Recently, obesity was determined to be associated with various pulmonary diseases including asthma, acute lung injury, and chronic obstructive pulmonary disease. However, how obesity contributes to pulmonary diseases and whether leptin directly regulates lung inflammation remains unclear. We used cell and animal models to study the mechanisms of leptin mediation of pulmonary inflammation. We found that leptin activated de novo synthesis of cytosolic phospholipase A2-α (cPLA2-α) in vitro in the lung alveolar type II cells, A549, and in vivo in ICR mice. Upregulated cPLA2-α protein was attenuated by pretreatment with an OB-R blocking antibody, U0126, SB202190, SP600125, Bay11-7086, garcinol, and p300 siRNA, suggesting roles of p42/p44 MAPK, p38 MAPK, JNK1/2, NF-κB, and p300 in leptin effects. Leptin enhanced the activities of p42/p44 MAPK, p38 MAPK, JNK1/2, and p65 NF-κB in a time-dependent manner. Additional studies have suggested the participation of OB-R, p42/p44 MAPK, and JNK1/2 in leptin-increased p65 phosphorylation. Furthermore, p300 phosphorylation and histone H4 acetylation were reduced by blockage of OB-R, p42/p44 MAPK, p38 MAPK, JNK1/2, and NF-κB in leptin-stimulated cells. Similarly, blockage of the MAPKs/NF-κB/p300 cascade significantly inhibited leptin-mediated cPLA2-α mRNA expression. Our data as a whole showed that leptin contributed to lung cPLA2-α expression through OB-R-dependent activation of the MAPKs/NF-κB/p300 cascade.

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Lung inflammation caused by adenosine-5′-triphosphate is mediated via Ca2+/PKCs-dependent COX-2/PGE2 induction

Cited by 22 publications

References 37 publications

AdipoR-increased intracellular ROS promotes cPLA₂and COX-2 expressions via activation of PKC and p300 in adiponectin-stimulated human alveolar type II cells

AdipoR-increased intracellular ROS promotes cPLA₂and COX-2 expressions via activation of PKC and p300 in adiponectin-stimulated human alveolar type II cells

EP1 receptor is involved in prostaglandin E2-induced osteosarcoma growth

Leptin Promotes cPLA2 Gene Expression through Activation of the MAPK/NF-κB/p300 Cascade

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Lung inflammation caused by adenosine-5′-triphosphate is mediated via Ca2+/PKCs-dependent COX-2/PGE2 induction

Cited by 22 publications

References 37 publications

AdipoR-increased intracellular ROS promotes cPLA2and COX-2 expressions via activation of PKC and p300 in adiponectin-stimulated human alveolar type II cells

AdipoR-increased intracellular ROS promotes cPLA2and COX-2 expressions via activation of PKC and p300 in adiponectin-stimulated human alveolar type II cells

EP1 receptor is involved in prostaglandin E2-induced osteosarcoma growth

Leptin Promotes cPLA2 Gene Expression through Activation of the MAPK/NF-κB/p300 Cascade

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AdipoR-increased intracellular ROS promotes cPLA₂and COX-2 expressions via activation of PKC and p300 in adiponectin-stimulated human alveolar type II cells

AdipoR-increased intracellular ROS promotes cPLA₂and COX-2 expressions via activation of PKC and p300 in adiponectin-stimulated human alveolar type II cells